Musculoskeletal, Skin, and Connective Tissue—Pharmacology

Disease-modifying antirheumatic drugs are antiinflammatory medications used to manage rheumatoid arthritis. The medications slow, but do not cure, the progression of the disease. The medications are classified as either synthetic or biologic agents and each has unique mechanisms of action and side effects. Common side effects among the disease-modifying antirheumatic drugs include bone marrow suppression and hepatotoxicity. Leflunomide, methotrexate, and tumor necrosis factor (TNF)-ɑ inhibitors are avoided in pregnancy due to their potential teratogenicity. Hydroxychloroquine and sulfasalazine are safe for use during pregnancy.

Nonsteroidal antiinflammatory drugs (NSAIDs) are a class of medications consisting of aspirin, reversible NSAIDs, and selective NSAIDs. NSAIDs are used as antiplatelet, analgesic, antipyretic, and antiinflammatory agents. Common side effects include GI irritation, prolonged bleeding, and AKI.

Eicosanoids are cell-signaling molecules produced from arachidonic acid. With the action of phospholipase A2, arachidonic acid is released from the plasma membrane. The different families of eicosanoids, which are prostaglandins (PGs), thromboxanes (TXA2s), prostacyclin (PGI2), lipoxins (LXs), and leukotrienes (LTs), emerge from a series of reactions catalyzed by different enzymes. The LTs and LXs are products of the lipoxygenase (LOX) pathway. The remaining eicosanoids are produced from the COX pathway, which involves 2 enzymes, COX-1 and COX-2. Eicosanoids are involved in various physiological and pathological processes. Thromboxanes cause platelet aggregation and are potent vasoconstrictors. Leukotrienes mediate allergic responses, while LXs have anti-inflammatory activities. Principal actions of PGs include vasodilation, smooth muscle contraction, and inflammation. Prostacyclin, a member of the PG family, has a potent vasodilatory effect. Both biologic actions and inhibitions of eicosanoids are mechanisms used in pharmacologic agents for various medical conditions and desired clinical effects.

Autoimmunity is a pathologic immune response toward self-antigens, resulting from a combination of factors: immunologic, genetic, and environmental. The immune system is equipped with self-tolerance, allowing immune cells such as T cells and B cells to recognize self-antigens and to not mount a reaction against them. Defects in this mechanism, along with environmental triggers (such as infections) and genetic susceptibility factors (most notable of which are the HLA genes) can lead to autoimmune diseases. These conditions are more commonly seen in women. Autoimmune diseases are chronic, with clinical manifestations consistent with the associated immune response. Among these conditions are Graves’ disease (autoantibodies against thyroid hormone receptors), myasthenia gravis (antibodies against acetylcholine receptors), type 1 diabetes (pancreatic β-cell destruction by immune cells), and systemic lupus erythematosus (multiorgan damage driven by immune complexes and autoantibodies).